Yawning is a poorly understood phenomenon
that occurs in humans as well as most
vertebrates(1). Yawns are slow, involuntary
gaping movements of the mouth that begin with a
slow inspiration and end with a larger
expiration (1). They are frequently but not
always associated with stretching (1). Yawning
bas been associated with boredom, fatigue,
sleepiness, a variety of pathologie states, and
many drugs. Dopamine agonists and cholinergic
agonists induce yawning (2,4) whereas
cholinergic receptor antagonists and dopamine
antagonists block this effect (5).

As best we could determine, yawning has not
been associated with treated or untreated
Parkinson's disease (PD). Since biochemical and
pharmacologic evidence points to a central role
for cholinergic and dopamaminergic mechanisms,
the occurrence of yawning in treated PD patients
may shed light on this poorly understood,
although possibly unimportant, phenomenon. We
were impressed by one patient's story-that his
"ons" were always preceded by yawns
although he was feeling neither sleepy nor more
alert. A second patient also volunteered a
similar yawning experience. We report
this phenomenon mostly for its theoretical
interest for the understanding of yawning.

Patient report : A 58-year-old man was
diagnosed with PD at age 44. He has been treated
with carbidopa-levodopa since age 47. Clinical
fluctuations in response to L-dopa began at age
50. Trials of pergolide, bromocriptine, and
amantadine were net tolerated. Sinemet
controlled release induced worsening
dyskinesias. When "on" the patient had good
mobility and walked independently. When "off" he
could not get up from a chair, tap his feet when
seated, or walk. He reported that the yawning
bad been an aura for turning "on" from
L-dopa since the age of 54. The yawns always
preceded turning "on," but voluntary yawning did
not induce air "on." The yawning generally
preceded turning "on" by 3 to 6 minutes and was
often associated with stretching. At the time
when his yawning was observed he was
taking carbidopa-levodopa 25/ 250 one-half
tablet every 60 to 90 minutes throughout the day
and most of the night. His last dose had been
about 15 minutes before. He took no other
medications. He was mobile for about 2 hours in
the morning, 2 hours in the afternoon, and 1
hour at night. He was observed in the "off"
state, unable for move his legs or to walk. He
yawned, without stretching, and denied
sleepiness or change in his level of alertness.
About 5 minutes later he suddenly turned "on,"
and was able to stand easily and walk without
difficulty. No dyskinesias were present.

Discussion.

Yawning is considered a primitive behavior
associated with changes in arousal levels, with
most yawning taking place during transitions
from sleeping to waking and from wakin. An
increase in yawning is a reliable predictor of
achange in arousal levels (6). However, yawning
may be only one of many mechanisms that cause a
change in level of alertness and may simply be a
marker of the change (an epiphenomenon) or a
mechanism to maintain some level of
activity(1,6).

The physiologic mechanism of yawning is
poorly understood. Anencephalics, having only a
brainstem and rudimentary midbrain structure,
still yawn, thus indicating that some neural
circuits necessary for yawning are most likely
near the respiration center in the medulla. The
neural mechanism probably involves both
respiratory and motor components, because
hemiplegics are unable to separate these acts.
In fact, hemiplegics
may perform involontary stretching movements
of their otherwise paralyzed arm while yawning.
Lesion experiments suggest that the Striatum is
critically involved in the yawning process.
Apomorphine when administered directly into the
caudate nucleus and the paraventricular nucleus,
induces yawning, suggesting that a central
dopaminergic system may be related to
yawning(2,4).

Based on experimental findings, the yawning
induced by cholinesterase inhibitors and
moscarinic receptor agonists involves
cholinergic activation alone. The yawning
responses to dopamine receptor agonists.- on the
other hand, seem to require both dopaminergic
and cholinergic activation, because muscarinic
receptor antagonists block yawning induced by
both dopamine and cholinergic agonists, whereas
dopamine receptor antagonists block only yawning
induced by dopamine agonists(5).

However, the pharmacology is far more
complicated than this. Various neuropeptides,
such as alpha melanocyte stimulating hormone and
oxytocin, will induce yawning when injected into
rat ventricles (7) This is increased by
pretreatment with pindolol, a
ß-adrenoreceptor antagonist, although
pindolol does itself induce yawning.
Oxytocinpindolol yawning is blocked by
scopolamine, an anticholinergic, but not by
spiperone, a dopamine-type receptor blocker(5)
In addition, a wide variety of drugs produce
yawning, as well as some drug withdrawal
syndromes.

If yawning is a dopamine-mediated phenomenon
in humans it should be seen in PD patients
treated with L-dopa and dopamine agonists. The
occurrence of the yawn is clearly a transient
phenomenon, signaling a change of state (always
"off" to "on"), but was not associated with a
change in level of arousal, at least as
perceived by the patients or by one author
(JHF). Our observations may lead to further
understanding of yawning, which may hopefully
have an impact on our understanding of the
dopamineacetylcholine systems in PD.